Molecular and Integrative Toxicology Claude L. Hughes Michael D. Waters Editors Translational Toxicology Defi ning a New Therapeutic Discipline Molecular and Integrative Toxicology Series editor Rodney R. Dietert, Department Microbiology & Immunology, Cornell University College of Veterinary Medicine, Ithaca, New York, USA Molecular and Integrative Toxicology presents state-of-the-art toxicology in a useful context. Volumes emphasize the presentation of cellular and molecular information aimed toward the protection of human or animal health or the sustainability of environmental systems. More information about this series at h ttp://www.springer.com/series/8792 Claude L. Hughes (cid:129) Michael D. Waters Editors Translational Toxicology Defi ning a New Therapeutic Discipline Editors Claude L. Hughes Michael D. Waters Therapeutic Science & Strategy Unit Michael Waters Consulting Quintiles, Inc. Hillsborough , NC , USA Morrisville , NC , USA Department of Obstetrics and Gynecology Duke University Medical Center Durham , NC , USA Department of Mathematics North Carolina State University Raleigh , NC , USA ISSN 2168-4219 ISSN 2168-4235 (electronic) Molecular and Integrative Toxicology ISBN 978-3-319-27447-8 ISBN 978-3-319-27449-2 (eBook) DOI 10.1007/978-3-319-27449-2 Library of Congress Control Number: 2016934930 Springer Cham Heidelberg New York Dordrecht London © Springer International Publishing Switzerland 2016 T his work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifi cally the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfi lms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. T he use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specifi c statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. T he publisher, the authors and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, express or implied, with respect to the material contained herein or for any errors or omissions that may have been made. Printed on acid-free paper Humana Press is a brand of Springer Springer International Publishing AG Switzerland is part of Springer Science+Business Media (www. springer.com) Pref ace W hile the scope, principles, and aims of the science of toxicology are broadly accepted, herein we are arguing that an even more expansive perspective is now needed. The modifi er “translational” in its current biomedical sense means expedit- ing research and development steps from basic science to human clinical studies with progression into therapeutic trials and iterative cycles of “lessons learned.” Juxtaposition of “translational” with “toxicology” is our novel and challenging effort to characterize the research and environmental and public health opportuni- ties that should exist for the development of protective, mitigative, or therapeutic interventions attributable to the human health impact of a wide range of environ- mental exposures. As microbiology is the basic science underpinning clinical infectious diseases, we see toxicology and environmental medicine as a corollary. In the realm of micro- biology, some infectious diseases are certainly best addressed by avoidance of expo- sure to the causative (infectious) agent. Since we live in a world in which we are intimately associated with and exposed to innumerable microorganisms, there are other inevitable exposures to infectious agents which sometimes do and sometimes do not cause clinical disease. The entire fi eld of antibiotic research focuses on developing therapeutic interventions that may be used acutely as courses of pharma- ceutical therapy to effect a true cure, or antimicrobial drugs may be used in a mitiga- tive matter to enhance human health by providing long-term suppression of clinical disease that would otherwise result from the antecedent exposure to the causative infectious agent. If we now set aside the infectious environmental agents, the other chemical, physical, nutritional, and social exposures also pose major exposure- related health risks. For these exposures, toxicology is arguably the relevant area of basic science, while environmental medicine and public health are the correspond- ing areas of clinical science. Some exposures to toxicologic agents should be avoided as the best means for preventing consequent associated injury or diseases. In clinical practice settings such as in Poison Control Centers where cases of acute intoxication are managed, clinicians implement interventions aimed at resolving the intoxication in order to save the individual from mortality or harm. However, as is the case for numerous infectious agents, many toxicant exposures are essentially v vi Preface unavoidable. In these nonacute instances, the toxicologic correlate to subacute, sub- chronic, or chronic infectious diseases has been largely ignored as an area of scien- tifi c research for therapeutic development. Given the certainty that gene-environment interactions are central to understanding human health and disease across the life span, we implore our readers to consider the erudite contributions of our multiple authors of the ensuing chapters and think deeply about the ways in which all of you may be able to contribute to making advances in this newly defi ned fi eld of scien- tifi c and medical research to enhance human health in the future. Durham and Morrisville, NC, USA Claude L. Hughes Hillsborough , NC , USA Michael D. Waters Contents Part I Introduction 1 The Opportunity to Translate Developmental Toxicology into a Therapeutic Discipline ................................................................. 3 Claude L. Hughes , Michael D. Waters , David Allen , and Iyabo Obasanjo 2 The Role of Toxicokinetics and Toxicodynamics in Developmental and Translational Toxicology .................................. 45 Edward L. Croom Part II Toxicant Modes of Action and Biomarkers 3 Mutational Effects ................................................................................... 85 Edward L. Croom 4 Ligand-Mediated Toxicology: Characterization and Translational Prospects ................................................................... 113 Rais Ansari , Claude L. Hughes , and Kazim Husain 5 Effects of Environmentally Acquired Heavy Metals and Nutrients on the Epigenome and Phenotype ................................. 139 David A. Skaar , Susan K. Murphy , and Cathrine Hoyo 6 Fetal Imaging and Effects of Exposures on Growth and Function ............................................................................................ 171 Elena Demicheva and Fatima Crispi vii viii Contents Part III Developmental Risks of Exposures and Potential Translational Toxicology Therapeutics 7 Ovarian Toxicity of Environmental Contaminants: 50 Shades of Grey .................................................................................... 215 M. A. Dominguez , J. C. Sadeu , M. T. Guerra , H. C. Furlong , Sharnjit Baines , and Warren G. Foster 8 The “Toxic” Effects of a Perinatal Obesogenic Environment: Maternal Obesity and Impacts on Future Generations ...................... 245 Leon Chalil and Deborah M. Sloboda 9 The Role of Environmental Exposures in Preterm Birth .................... 269 Kelly K. Ferguson and John D. Meeker 10 The Impact of Environmental Stressors on DNA Methylation, Neurobehavioral Development, and Chronic Physical Aggression: Prospects for Early Protective Interventions ......................................................... 295 Richard E. Tremblay , Linda Booij , Nadine Provençal , and Moshe Szyf 11 Coffee Health Effects from Early Fetal Development Through Childhood and Adolescence ................................................... 321 Roseane Maria M. Santos and Darcy Roberto A. Lima 12 Ethical Considerations in Development of Future Therapies for Women and Children ...................................................... 339 Toby Schonfeld Index ................................................................................................................. 373 Co ntributors David Allen Science and Strategy , Integrated Laboratory Systems, Inc. (ILS) , Durham , NC , USA Rais Ansari Department of Pharmaceutical Sciences, College of Pharmacy , Nova Southeastern University , Fort Lauderdale , FL , USA Sharnjit Baines Department of Obstetrics & Gynaecology , McMaster University , Hamilton , ON , Canada Linda Booij Department of Psychology , Concordia University , Montreal , QC , Canada CHU Sainte-Justine , Montreal , QC , Canada Leon Chalil D epartment of Biochemistry and Biomedical Sciences, Obstetrics and Gynecology, and Pediatrics , McMaster University , Hamilton , ON , Canada Fatima Crispi B CNatal | Barcelona Center for Maternal Fetal and Neonatal Medicine , Hospital Clínic and Hospital Sant Joan de Déu, Universitat de Barcelona , Barcelona , Spain Edward L. Croom BOV Solutions, INC , Statesville , NC , USA Elena Demicheva BCNatal | Barcelona Center for Maternal Fetal and Neonatal Medicine , Hospital Clínic and Hospital Sant Joan de Déu, Universitat de Barcelona , Barcelona , Spain M. A. Dominguez Facultad de Medicina Veterinaria y Zootecnia , Universidad Autónoma de Tamaulipas , Cd. Victoria , Tamaulipas , Mexico Kelly K. Ferguson Department of Environmental Health Sciences , University of Michigan School of Public Health , Ann Arbor , MI , USA Warren G. Foster Department of Obstetrics & Gynaecology , McMaster University , Hamilton , ON , Canada ix